Increased Plasma Histamine Levels Research Articles

Melanotan II causes hypothermia in mice by activation of mast cells and stimulation of histamine 1 receptors.

Intraperitoneal administration of the melanocortin agonist melanotan II (MTII) to mice causes a profound, transient hypometabolism/hypothermia. It is preserved in mice lacking any one of melanocortin receptors 1, 3, 4, or 5, suggesting a mechanism independent of the canonical melanocortin receptors. Here we show that MTII-induced hypothermia was abolished in KitW-sh/W-sh mice, which lack mast cells, demonstrating that mast cells are required. MRGPRB2 is a receptor that detects many cationic molecules and activates mast cells in an antigen-independent manner. In vitro, MTII stimulated mast cells by both MRGPRB2-dependent and -independent mechanisms, and MTII-induced hypothermia was intact in MRGPRB2-null mice. Confirming that MTII activated mast cells, MTII treatment increased plasma histamine levels in both wild-type and MRGPRB2-null, but not in KitW-sh/W-sh, mice. The released histamine produced hypothermia via histamine H1 receptors because either a selective antagonist, pyrilamine, or ablation of H1 receptors greatly diminished the hypothermia. Other drugs, including compound 48/80, a commonly used mast cell activator, also produced hypothermia by both mast cell-dependent and -independent mechanisms. These results suggest that mast cell activation should be considered when investigating the mechanism of drug-induced hypothermia in mice.

Investigation of peanut oral immunotherapy with CpG/peanut nanoparticles in a murine model of peanut allergy

Treatments to reverse peanut allergy remain elusive. Current clinical approaches using peanut oral/sublingual immunotherapy are promising, but concerns about safety and long-term benefit remain a barrier to wide use. Improved methods of delivering peanut-specific immunotherapy are needed. We sought to investigate the efficacy and safety of peanut oral immunotherapy using CpG-coated poly(lactic-co-glycolic acid) nanoparticles containing peanut extract (CpG/PN-NPs) in a murine model of peanut allergy. C3H/HeJ mice were rendered peanut allergic by means of oral sensitization with peanut and cholera toxin. Mice were then subjected to 4 weekly gavages with CpG/PN-NPs, vehicle (PBS), nanoparticles alone, peanut alone, CpG nanoparticles, or peanut nanoparticles. Untreated mice served as naive controls. After completing therapy, mice underwent 5 monthly oral peanut challenges. Anaphylaxis was evaluated by means of visual assessment of symptom scores and measurement of body temperature and plasma histamine levels. Peanut-specific serum IgE, IgG1, and IgG2a levels were measured by using ELISA, as were cytokine recall responses in splenocyte cultures. Mice with peanut allergy treated with CpG/PN-NPs but not vehicle or other treatment components were significantly protected from anaphylaxis to all 5 oral peanut challenges, as indicated by lower symptom scores, less change in body temperature, and a lower increase of plasma histamine levels. Importantly, CpG/PN-NP treatment did not cause anaphylactic reactions. Treatment was associated with a sustained and significant decrease in peanut-specific IgE/IgG1 levels and an increase in peanut-specific IgG2a levels. Compared with vehicle control animals, peanut recall responses in splenocyte cultures from nanoparticle-treated mice showed significantly decreased levels of TH2 cytokines (IL-4, IL-5, and IL-13) but increased IFN-γ levels in cell supernatants. Preclinical findings indicate that peanut oral immunotherapy with CpG/PN-NPs might be a valuable strategyfor peanut-specific immunotherapy in human subjects.

D-dimer and histamine in early stage bacteremia: A prospective controlled cohort study

IntroductionPlasma histamine levels and D-dimer predict disease severity and mortality in advanced septic shock. We hypothesized that increased plasma histamine levels parallel coagulation activation and yield prognostic significance already at a very early stage of bacteremia. Patients and methodsThis prospective controlled cohort study enrolled 72 consecutive non-surgical non-ICU-ward inpatients with newly culture-diagnosed bacteremia and a Pitt Bacteremia score ≤2 to determine the extent of histamine and D-dimer release and their predictive role on outcome at the earliest stage of blood stream infection. Age-matched healthy adults served as internal controls (n=36). A binominal logistic regression and a Cox proportional hazards regression analysis were performed to ascertain the effects of D-dimer and histamine on in-hospital mortality. ResultsIn contrast to plasma histamine, D-dimer levels were significantly higher within hours of culture-proven bacteremia. In-hospital mortality occurred in 17%. Histamine levels were neither associated with D-dimer level (r=0.04; p>0.05) nor with ICU admissions (r=0.06; p>0.05) and outcome (crude OR 0.8, 95% CI 0.3–1.9; p=0.6). In contrast, early-elevated D-dimer levels predicted mortality: the odds to die increased with the D-dimer level, and was 12.6 (crude OR, 95% CI 3–52; p=0.001) in patients with a D-dimer ≥4μg/mL (n=13). ConclusionHistamine levels are elevated in only few patients (4%) with newly diagnosed bacteremia. Our findings suggest that D-dimer, but not plasma histamine, could be a promising marker of lethality already at a very early stage of blood stream infection.

Adverse skin reactions to iodinated x-ray contrast agents in healthy rats.

The aim of this preclinical study on healthy Sprague-Dawley rats was to determine whether differences exist in the induction of adverse skin reactions after the intravenous administration of a monomeric and 2 dimeric iodinated nonionic contrast agents. After intravenous injection of iopromide (monomeric), iodixanol (dimeric), and iotrolan (dimeric) at a dose of 4 g iodine/kg of body weight, mechanical ear volume measurements (10 minute after injection) and intravital microscopy (baseline, 5 minutes after injection) of the ear with the near-infrared dye indocyanine green were performed to determine the volume change and plasma extravasation. Histopathological analysis (20 minutes, 1 hour, and 3 hours after injection) was performed to diagnose alterations in the skin. Blood plasma was analyzed to identify elevated levels of histamine (5 minutes after injection) and inflammatory markers (a multianalyte profile of 58 markers; 1 hour and 3 hours after injection). Only iodixanol induced immediate angioedema formation, with a 100% incidence rate and with slight mast cell infiltration in the ear, muzzle, and paws. The ear showed a 53% volume increase and strong extravasation of plasma proteins into the interstitium, which correlated with highly (11-fold) increased plasma histamine levels 5 minutes after injection. Elevated levels of tumor necrosis factor-α (7.1-fold), macrophage inflammatory protein (MIP)-1α (3.2-fold), and MIP-2 (7.7-fold) were identified 1 hour after the iodixanol injection. Increased levels (fold-change) of MIP-1β (14; 6.3), monocyte chemotactic protein-1 (3.3; 3.7), monocyte chemotactic protein-3 (2.4; 3.0), stem cell factor (1.7; 2), vascular endothelial growth factor (2; 2.1), and interferon gamma-induced protein-10 (4.1; 39.1) were identified 1 hour and 3 hours after the iodixanol administration, respectively. The level of these molecules remained unchanged after the iopromide and iotrolan injections (except for stem cell factor). A reversible anaphylactoid-like reaction in healthy Sprague-Dawley rats was observed after the iodixanol administration but not after the monomeric iopromide or dimeric iotrolan injections. Therefore, we conclude that the induction of adverse skin reactions is not per se because of a class effect of dimeric contrast agent.

Interaction of SSR161421, a novel specific adenosine A3 receptor antagonist with adenosine A3 receptor agonists both in vitro and in vivo

A novel adenosine A3 receptor antagonist (SSR161421) was characterized by both receptor binding assays and pharmacological tests. Binding studies on cloned human adenosine receptors showed that SSR161421 has high affinity for adenosine hA3 receptors (Ki=0.37nM) with at least 1000-fold selectivity compared to hA1, hA2A and hA2B receptors. The receptor antagonist nature of SSR161421 was determined in a functional study on Chinese hamster ovarian cells (CHO) cells expressing human adenosine A3 receptors. SSR161421 competitively antagonized the effect of 2-chloro-N6-(3-iodobenzyl)-adenosine-5′-N-methylcarboxamide (Cl-IB-MECA) on cAMP production with a pA2 value in a luciferase reporter gene construct. In mice, intravenously administered SSR161421 inhibited the N6-(4-aminobenzyl)-adenosine-5′-N-methyl-uronamide dihydrochloride (AB-MECA) induced increase in plasma histamine levels (ED50=2.0mg/kg) and the Cl-IB-MECA evoked plasma extravasation (ID50=2.9mg/kg) and oedema formation (ID50=4.6mg/kg) in mouse ear.

Sensitization to acid‐hydrolyzed wheat protein by transdermal administration to BALB/c mice, and comparison with gluten

An increasing number of studies have shown that hydrolyzed wheat protein (HWP) can induce IgE-mediated hypersensitivity by skin contact and/or food ingestion. However, there has been no study of the sensitizing potential of HWP. In this study, the possibility of transdermal pathway for sensitization to acid-HWP (HWP1) was investigated using BALB/c mice, and compared with that of gluten. HWP1 or gluten (500μg/mouse) was transdermally administered using patches. After three or four cycles of sensitization for 3days/week, active systemic anaphylaxis (ASA) was induced by intraperitoneal injection of the antigen, and rectal temperatures, scores of anaphylactic responses, and plasma histamine levels were determined. Because HWP1 was included in facial soap in Japan, the effect of detergent on the sensitizing potential was also investigated. Transdermal administration of HWP1 induced dose-dependent production of IgE and IgG1. After sensitization for 3 or 4weeks, intraperitoneal injection of HWP1 caused ASA, leading to decreased rectal temperatures, increased anaphylaxis scores, and increased plasma histamine levels. In addition, splenocytes harvested after ASA produced IL-4, IL-5, and IL-10 by re-stimulation with HWP1. Transdermal exposure to gluten also induced IgE and IgG1 production, and intraperitoneal injection of gluten also induced ASA only in mice sensitized in the presence of sodium dodecyl sulfate. Transdermal exposure to HWP1 is sufficient to activate key immune pathways necessary for sensitizing mice for immediate hypersensitivity reactions. This study shows that HWP has a sensitizing potential as well as gluten, whereas its allergenicity may be different from that of gluten.

Expression of organic cation transporter 3 (SLC22A3) and plasma membrane monoamine transporter (SLC29A4) in human umbilical vein endothelial cells and their relevance for histamine uptake

Background Increased plasma histamine levels lead to pathological events. Endothelial cells actively participate in histamine clearance by promoting its uptake via yet unidentified carriers, thus limiting histamine effects. The organic cation transporter 3 (OCT3) and plasma membrane monoamine transporter (PMAT) are the two most prominent transporters for endogenous monoamines. OCT3 and PMAT show Na/K-ATPase independency. Both are highly sensitive to inhibition by the isocyanine compound, decynium-22. However, OCT3 is highly sensitive to corticosteron, whereas PMAT is not. We showed in the past that decynium-22 inhibits histamine uptake in cultured human umbilical vascular endothelial cells (HUVEC). In the present study we identified the expression of OCT3 and PMAT in freshly isolated and cultured HUVEC as well as some characteristics of histamine uptake in cultured HUVEC such as ouabain and corticosteron sensitivity.

Chinese herbal extracts of Rubia cordifolia and Dianthus superbus suppress IgE production and prevent peanut-induced anaphylaxis

BackgroundPeanut allergy is characterized by increased levels of peanut-specific IgE in the serum of most patients. Thus, the most logical therapy would be to inhibit the IgE production by committed B-cells. This study aims to investigate the unreported anti-IgE effects of Chinese herbal extracts of Rubia cordifolia (Qiancao) and Dianthus superbus (Qumai).MethodsSeventy herbal extracts were tested for their ability to reduce IgE secretion by a human B-cell line. Those with the lowest inhibitory concentration 50 (IC50) values were tested in a mouse model of peanut-anaphylaxis. Anaphylactic scores, body temperature, plasma histamine and peanut-specific-immunoglobulins were determined.ResultsRubia cordifolia and Dianthus superbus inhibited the in vitro IgE production by a human B-cell line in a dose-dependent manner and the in vivo IgE production in a murine model of peanut allergy without affecting peanut-specific-IgG1 levels. After challenge, all mice in the sham groups developed anaphylactic reactions and increased plasma histamine levels. The extract-treated mice demonstrated significantly reduced peanut-triggered anaphylactic reactions and plasma histamine levels.ConclusionThe extracts of Rubia cordifolia and Dianthus superbus inhibited the IgE production in vivo and in vitro as well as reduced anaphylactic reactions in peanut-allergic mice, suggesting potentials for allergy treatments.

Enhancement of Gastrointestinal Absorption of Ovalbumin Caused by Spermine Induces an Increase in Plasma Histamine Levels in Mice Sensitized to Ovalbumin

The aim of this study was to determine whether a spermine (SPM)-induced increase in gastrointestinal absorption of an allergen leads to an anaphylactic response in sensitized mice. First, we examined the enhancing effect of SPM on the gastrointestinal absorption of ovalbumin (OVA) in an in situ jejunum loop study in rats and an in vivo oral absorption study in mice. Second, we investigated whether enhancement of gastrointestinal absorption of OVA caused by SPM induces an anaphylactic response in mice sensitized to OVA. In the in situ jejunum loop study in rats, a significant amount of immune-reactive OVA was detected in the plasma after co-administration of OVA and SPM. Oral co-administration of OVA and SPM to mice in vivo also increased plasma OVA concentrations in an SPM dose-dependent manner. Furthermore, in sensitized mice, a significant increase in plasma histamine levels occurred along with the increase in plasma OVA levels after co-administration of OVA with SPM. This finding suggests that an SPM-induced increase in gastrointestinal absorption of OVA leads to an anaphylactic response. These results indicate that excess oral ingestion of SPM may have widespread health effects, including the induction of food allergies, via modulation of the function of the gastrointestinal epithelial barrier.

Involvement of the organic cation transporters in histamine uptake into human vascular endothelial cells

Increased plasma histamine levels lead to pathological events. Endothelial cells actively participate in histamine clearance by promoting its rapid uptake [1, 2, 3] via yet unidentified carrier(s), thus limiting the spread of the histamine signal. Since histamine is a substrate for organic cationic transporters (OCT2 andOCT3) [4], andOCT3 is expressed in human blood vessels [5], the objectivewas to test whether OCT2 and/or OCT3 is/are involved in the clearance of histamine by human umbilical vein endothelial cells (HUVEC).

Therapeutic Effect of Topical Gamma-Linolenic Acid on Refractory Uremic Pruritus

Pruritus is a bothersome symptom affecting up to 80% of dialysis patients. Lymphocyte and cytokine interaction has an important role in the pathogenesis of uremic pruritus. Gamma-linolenic acid (GLA) is associated with immune modulation of T lymphocytes and lymphokines. The aim of this study is to determine whether topical GLA can attenuate uremic pruritus. Seventeen dialysis patients with refractory uremic pruritus who passed the screening criteria entered a prospective, randomized, double-blind, placebo-controlled, crossover study. They stopped all antipruritic therapy at least 2 weeks before the study and were randomly assigned to treatment with either GLA 2.2% cream or placebo-based cream applied to the entire body after taking a bath once a day and to pruritic sites 3 times a day for 2 weeks, and then the reverse treatment after a 2-week washout period. Severity of pruritus was evaluated by using a traditional visual analogue scale (VAS) and a modified questionnaire method (pruritus score [PS]). Hemogram, aspartate and alanine aminotransferases, bilirubin, albumin, blood urea nitrogen, creatinine, calcium, phosphate, and intact parathyroid hormone were measured. Sixteen patients completed the study; 1 patient was withdrawn because of an allergic skin reaction. There were no significant differences between groups except for sex distribution. Median VAS and PS values between groups did not differ significantly at baseline. There is a greater antipruritic effect of GLA based on evaluation with both the VAS and PS. There is persistence of a residual effect into the second treatment period after GLA treatment. GLA-rich cream is better than placebo-based cream for alleviating uremic pruritus. It is a useful adjuvant in the management of refractory uremic pruritus.

The A 3 AR agonist CP‐532,903 provides protection in two different mouse models of ischemia/reperfusion injury

The goal of this study was to determine the effect of the selective A3 adenosine receptor (AR) agonist CP-532,903 (CP) in an in vivo mouse model of infarction and an isolated mouse heart model of global ischemia/reperfusion injury (I/R). In vitro assays conducted with HEK 293 cells expressing recombinant mouse ARs determined that CP binds to the mouse A3AR with high affinity (9.6±2.5 nM) and displays greater selectivity compared to other commonly used A3AR agonists including IB-MECA and Cl-IB-MECA. Infarct size in control mice subjected to 30 min of left anterior descending coronary occlusion and 24 h of R was 57±2% of the area at risk (AAR). In mice pretreated 5 min before coronary occlusion with 30 or 100 μg/kg of CP, infarct size was reduced to 43% and 39% of the AAR, respectively. Administration of CP produced a short-lived reduction in mean arterial blood pressure and significantly increased plasma histamine levels, responses likely due to A3AR-mediated degranulation of mast cells. In the isolated heart studies, coronary infusion of 10, 30 or 100 nM CP for 10 min prior to 20 min of global I and 45 min of R produced a concentration-dependent improvement in recovery of left ventricular developed pressure and +/-dP/dt (~30% at 100 nM) compared to vehicle-treated mice. In contrast to the in vivo studies, infusion of CP in isolated hearts produced no changes in hemodynamic parameters. The selectivity of CP in the two mouse models was confirmed by repeating the studies using A3AR gene knock-out mice. We conclude that the A3AR agonist CP provides protection against I/R injury in mouse hearts by activating the A3AR. NRSA Fellowship #1F32HL073643-01A1

Evaluation of histamine release during constant rate infusion of morphine in dogs

Previous studies have reported increased plasma histamine levels after single intravenous injections of morphine in dogs. The goals of this study were to evaluate histamine release and selected physiologic parameters during constant rate infusion (CRI) of morphine in dogs. Five adult healthy, conscious, intact female dogs were studied. Using a Latin square, repeated-measures design, dogs were randomly assigned to three treatment groups to receive either a loading dose of morphine at 0.3 mg kg−1 IV followed by a CRI of 0.17 mg kg−1 hour−1 IV (LM) or 0.6 mg kg−1 IV followed by a CRI of 0.34 mg kg−1 hour−1 IV (HM) or a bolus and a CRI of saline (SAL). Dogs received each of the three treatments at intervals of at least 7 days. Plasma histamine concentrations, skin flushing, edema and wheals, heart rate and rhythm and noninvasive arterial blood pressure were measured before and at 1, 2, 5, 15, 30, 60, 120, 180 and 240 minutes during the CRI or at the time of occurrence. Observer was blinded to the treatment given. Results showed that the highest histamine release occurred in the HM group at 1 minute after the loading dose (median 10.6 ng mL−1), which was significantly different from the LM (median 1.85 ng mL−1) and the SAL (median 0.26 ng mL−1) groups. By comparison, no other significant differences in plasma histamine were seen for the remaining time points, although during the CRI, plasma histamine levels were numerically highest in the LM group. One dog that developed hypotension for two minutes after the loading dose in the HM group and one dog showed occasional ventricular premature contractions during both morphine CRIs, otherwise cardiovascular parameters were similar among the three treatment groups. In conclusion, both doses of morphine induced variable histamine release with minimal cardiovascular adverse effects in these awake, healthy dogs. The plasma histamine levels obtained may be associated with significant hemodynamic changes in patients with limited cardiovascular reserve and reduced sympathetic tone.

The Chinese herbal medicine formula FAHF-2 completely blocks anaphylactic reactions in a murine model of peanut allergy

Peanut allergy is potentially life threatening. There is no curative therapy for this disorder. We previously found that an herbal formula, food allergy herbal formula (FAHF)-1, blocked peanut-induced anaphylaxis in a murine model when challenged immediately posttherapy. To test whether FAHF-2, an improved herbal formula, from which 2 herbs, Zhi Fu Zi (Radix Lateralis Aconiti Carmichaeli Praeparata) and Xi Xin (Herba Asari), were eliminated, is equally effective to FAHF-1, and if so, whether protection persists after therapy is discontinued. Mice allergic to peanut treated with FAHF-2 for 7 weeks were challenged 1, 3, or 5 weeks posttherapy. Anaphylactic scores, core body temperatures, vascular leakage, and plasma histamine levels after peanut challenge were determined. Serum peanut-specific antibody levels and splenocyte cytokine profiles were also measured. After challenges, all sham-treated mice developed severe anaphylactic signs, significant decrease in rectal temperatures, significantly increased plasma histamine levels, and marked vascular leakage. In contrast, no sign of anaphylactic reactions, decrease in rectal temperatures, or elevation of plasma histamine levels was observed in FAHF-2-treated mice in 5 separate experiments. IgE levels were significantly reduced by FAHF-2 treatment and remained significantly lower as long as 5 weeks posttherapy. Splenocytes from FAHF-2-treated mice showed significantly reduced IL-4, IL-5, and IL-13, and enhanced IFN-gamma production to recall peanut stimulation in vitro . FAHF-2 treatment completely eliminated anaphylaxis in mice allergic to peanut challenged as long as 5 weeks posttherapy. This result was associated with downregulation of T H 2 responses. FAHF-2 may be a potentially effective and safe therapy for peanut allergy.

Genetic susceptibility to food allergy is linked to differential TH2-TH1 responses in C3H/HeJ and BALB/c mice

Background: Although food allergy is a serious health problem in westernized countries, factors influencing the development of food allergy are largely unknown. Appropriate murine models of food allergy would be useful in understanding the mechanisms underlying food allergy in human subjects. Objective: We sought to determine the susceptibility of different strains of mice to food hypersensitivity. Methods: C3H/HeJ and BALB/c mice were sensitized to cow's milk (CM) or peanut by means of intragastric administration, with cholera toxin as a mucosal adjuvant. Mice were then challenged with CM or peanut. Antigen-specific IgE levels, anaphylactic symptoms, plasma histamine levels, and splenocyte cytokine profiles of these 2 strains were compared. Results: CM-specific IgE levels were significantly increased only in the C3H/HeJ strain, 87% of which exhibited systemic anaphylactic reactions accompanied by significantly increased plasma histamine levels in response to challenge. BALB/c mice exhibited no significant CM-specific IgE response, increased plasma histamine levels, or anaphylactic symptoms. After peanut challenge, 100% of peanut-sensitized C3H/HeJ mice exhibited high levels of peanut-specific IgE and anaphylactic symptoms. In contrast, no hypersensitivity reactions were detected in BALB/c mice, despite the presence of significant serum peanut-specific IgE levels. Splenocytes from CM- and peanut-sensitized C3H/HeJ mice exhibited significantly increased IL-4 and IL-10 secretion, whereas splenocytes from BALB/c mice exhibited significantly increased IFN-γ secretion. Conclusion: Induction of food-induced hypersensitivity reactions in mice is strain dependent, with C3H/HeJ mice being susceptible and BALB/c mice being resistant. This strain-dependent susceptibility to food allergy is associated with differential TH2-TH1 responses after intragastric food allergen sensitization. (J Allergy Clin Immunol 2003;111:1122-8.)

Role of endogenous histamine in altered lung mechanics in rabbits.

Unlike the effects of exogenous histamine, those of endogenous histamine on the lung mechanics have not yet been characterized. The site of endogenous histamine liberation by mivacurium was determined, as were the effects of this histamine on the airway and parenchymal mechanics in control rabbits (group C) and rabbits pretreated with H1 and H2 receptor blockers (group AH). The effectiveness of the receptor blockade was ensured by challenges with exogenous histamine. Pulmonary input impedance at low frequencies (ZL) was measured in anesthetized mechanically ventilated open-chest rabbits under control conditions and every minute after administration of an intravenous bolus of mivacurium (2 mg/kg) and exogenous histamine (10 microg/kg). Histamine levels were determined in serum samples taken from the carotid artery and jugular vein before and 1, 3, and 6 min after mivacurium injection. Parameters of airway resistance (Raw) and inertance and parenchymal damping (G) and elastance (H) were extracted from ZL spectra. Mivacurium induced significant increases in plasma histamine levels, with the venous concentrations being significantly higher than those in the artery. The mivacurium-induced increase in Raw (28.7 +/- 2.3%; mean +/- SD) in group C was significantly higher than that in group AH (6.6 +/- 3.4%), whereas the responses in G were not inhibited significantly (23.9 +/- 6.9% vs. 15.5 +/- 3.0%). The significant increases in Raw (70.6 +/- 12.6%) and G (21.0 +/- 4.9%) after exogenous histamine administration were virtually completely abolished by antihistamine pretreatment (3.6 +/- 3.7% and 0.3 +/- 2.6%). After mivacurium administration, endogenous histamine is liberated at least partly in the systemic circulation, and it induces primarily a heterogeneous airway constriction with minor changes in the parenchymal properties. This response was considerably reduced but not abolished by antihistamine pretreatment, a circumstance suggesting that mivacurium may liberate other constrictor mediators that might also contribute to the airway and parenchymal constriction.

Effects of mirtazapine on the levels of exogenous histamine in the plasma of the cat.

Effects of the antidepressant drug mirtazapine on plasma levels and on the kinetics of injected histamine were studied in the cat. In the dose of 0.6 mg/kg mirtazapine did not affect the characteristics of the elimination curve of histamine. The higher dose of mirtazapine (1.2 mg/kg) prevented the increase of plasma histamine levels.

No correlation between wine intolerance and histamine content of wine

Background: Histamine is thought to be the main cause of adverse reactions to wines. Objective: The purpose of this study was to test the hypothesis that the level of histamine in wine affects the tolerance to wine in 16 subjects with wine intolerance. Methods: We performed a study to examine the effects of wine histamine content in 16 adults with wine intolerance. Each subject underwent 2 double-blind provocation tests with wine: 1 with a wine poor in histamine (0.4 mg/L), and 1 with a wine rich in histamine (13.8 mg/L). Blood was collected for histamine and methylhistamine RIAs at 0, 10, 30, and 45 minutes after ingestion of the wine. Methylhistamine and methylimidazolacetic acid (gas chromatography and mass spectrometry) were measured in urine 5 hours before and 5 hours after ingestion. Results: No significant differences in the occurrence of adverse reactions were noted after ingestion of either of the wines (McNemar test). At 10 minutes, a significant increase was observed in plasma histamine with histamine-poor wine. No significant changes (Wilcoxon test) were observed in the methylhistamine and methylimidazolacetic acid levels after ingestion of either histamine-poor or histamine-rich wine. Conclusion: This study demonstrates that there is no correlation between the histamine content of wine and wine intolerance. The increase of plasma histamine levels at 10 minutes with histamine-poor wine suggested the role of a histamine-releasing substance. The role of acetaldehyde is discussed. (J Allergy Clin Immunol 2001;107:375-8.)

Efeito da histamina na regeneração hepática: estudo experimental em ratos

Muitas substâncias têm sido utilizadas após hepatectomias parciais a fim de conhecer como elas atuam sobre o processo de regeneração hepática. Adequado fluxo sangüíneo parece ter muita importância neste processo. Autores descreveram, após hepatectomias em ratos, elevação dos níveis plasmáticos de histamina. Substâncias inibidoras da histidina-decarboxilase e da histaminase leva a elevação da histamina endógena com vasodilatação sinusoidal e aceleração da regeneração hepática. No presente estudo busca-se conhecer a influência da histamina exógena administrada à ratos parcialmente hepatectomizados. Utilizaram-se 32 ratos Wistar que sofreram hepatectomia de aproximadamente 67% da víscera. Os animais do grupo experimento receberam por via subcutânea 0,5 mg/Kg/dia de histamina e os do grupo controle igual volume de solução salina isotônica. As aferições foram realizadas com 36 horas e 7 dias. A avaliação do peso da víscera não mostrou diferença entre os grupos. O número de figuras de mitose em 10 campos foi maior no grupo experimento com 36 horas (p=0,010). No sétimo dia o número delas era semelhante nos dois grupos. Concluiu-se que a administração de histamina exógena, talvez pela sua vida média curta, aumenta o número de figuras de mitose no início do processo, não interferindo na regeneração ao final de 7 dias.

The Effects of Rapacuronium on Histamine Release and Hemodynamics in Adult Patients Undergoing General Anesthesia

Neuromuscular blocking drugs may have variable effects on heart rate (HR) and blood pressure.Rapacuronium is a rapid-acting, steroidal-derived neuromuscular blocking drug whose hemodynamic effects have not been characterized. We studied the effects of 1, 2, and 3 mg/kg rapacuronium on histamine release, HR, and blood pressure in 47 ASA physical status II or III adult patients after the induction of anesthesia with etomidate/fentanyl/N2 O. Plasma histamine concentrations were measured before induction and immediately before and 1, 3, and 5 min after the rapid administration of rapacuronium. Mean arterial pressure (MAP) decreased after rapacuronium administration, but there were no significant differences among the groups for changes in HR or MAP, and there was no correlation between changes in MAP or HR and increases in histamine levels. There were no changes in HR or MAP among five patients who had significant (>or=to1 ng/mL) increases in histamine from baseline. Seven patients had bronchospasm without increases in plasma histamine levels. Rapacuronium 2-3 mg/kg increased plasma histamine levels. However, clinically significant histamine-related sequelae did not occur in this population with 1- to 3-mg/kg doses of rapacuronium, and cardiovascular changes were not directly correlated with histamine release. Rapacuronium administration can produce hypotension via mechanisms that do not seem to be related to histamine release. Implications: Rapacuronium, a new steroidal-derived muscle relaxant, may release histamine and produce slight changes in blood pressure and heart rate after administration. (Anesth Analg 1999;89:290-5)